KOMINOX
1Features & Advantage
Category Description
Identification Kml001 (Kominox)
Chemicals name Sodium metaarsenite
Molecular formula NaAsO2
Molecular weight 129.9 g/mol
Purity > 99.8%
Solubility at water > 98 %
Biosorb rate more then 94.5%

Kominox is an arsenic-based new oral drug. There might be AsO2- ion in drinking water, sea weeds and plants. Compared to arsenic oxides such as As2O3, Kominox showed excellent tolerability. Kominox exerts anticancer activity and cancer pain-relieving efficacy by regulating gene expression and signal pathways in human body. The effectiveness is being verified in several non-clinical or clinical studies.

Arsenic as a chemical element (symbol As) occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. Arsenic trioxide (As2O3) can be generated via routine processing of arsenic compounds including the oxidation (combustion) of arsenic and arsenic-containing minerals in air.

2 As2S3 (orpiment)+ 9 O2 → 2 As2O3 + 6 SO2

Although As2O3 (or As2O6) was developed and used as an anti-cancer therapeutic, it is not popular because of its severe toxicities.

2Differences

Kominox is a relatively safe drug with very high water solubility compared with arsenic trioxide. According to X-ray crystallography data, these two materials have completely different molecular structures.

X-ray crystallographic data from Acta Cryst. (2004). C60, m215-m218

X-ray crystallographic data from P. Ballirano, A. Maras (2002). Refinement of the crystal structure of arsenolite, As2O3

3Mechanism
  • Cancer cells are those that have undergone abnormal mutations that cause rapid cell division
  • Early stage cancer cells are sometimes short-lived due to the erosion of telomeres caused by rapid cell division
  • Such shortening of telomeres causes cancer cells to die prematurely and be eliminated
  • However, malignant cancer cells produce telomerase, which is an enzyme that inhibits telomere shortening, allowing cancer cells continue to grow and divide.
  • Thus, telomerase is a key factor in cancer pathology and KOMIPHARM considers telomerase to be an important target in cancer therapy
  • KOMIPHARM’S new drug (NaAsO₂) eliminates cancer cells by selectively binding to telomeres of cancer cells
  • NaAsO₂ can treat cancer with minimal side effects because of its special molecular structure and high affinity for cancer cells with characteristically shortened telomeres, while healthy cells are unaffected (Telomeric Sequences and Erosion paper)

Telomere shortening by Kominox

4Mechanism
  • Current cytotoxic anticancer agents primarily kill mature cancer cell populations but cannot eradicate cancer stem cells. As a result, the cancer recurs in the form of metastatic cancer and the tumor consists of more aggressive cancer stem cells.
  • In order to treat metastatic cancer, a therapeutic agent capable of removing both mature cancer cells and cancer stem cells is essential.
  • Scientific studies have shown that the role of cancer stem cells in the occurrence of metastatic cancer is close to 100%.
  • Kominox, which we are developing, has the ability to kill 99% of the cancer stem cells of metastatic cancers metastasized from cancer cells sensitive to primary cancers.
5Anti- tumor effect

Antitumor effect of Kominox in a xenograft nude mouse model

6Anti- tumor effect

Results of 200 cancer cell killing experiments conducted to measure anticancer effects of
new drugs by using nano-technology testing method by national research institutes in Australia

1Phase II Clinical Trial on 14 metastatic cancers, including Brain metastases and Lung cancer (PJ Code: PAX-1-003)

RATIONALE

  • Currently available cytotoxic anticancer drugs primarily target mature cancer cells. They do not target cancer stem cells, which are the progenitors of highly proliferating cancer cells. Hence, currently available drugs are limited in controlling the spread of metastatic and recurrent cancers in mammals with immune systems (Karmanos paper, Capacity of cancer stem cells).
  • Cancer stem cells eventually lead to malignant metastatic cancers. Cancer stem cells must be eliminated to effectively treat metastatic cancers.
  • KOMIPHARM’S research indicates that cancer stem cells are responsible in nearly all cases of metastatic cancer pathologies. The new drug (PAX-1) being developed by KOMIPHARM eliminates 99% of cancer stem cells that lead to metastatic cancer (Karmanos paper, Capacity of cancer stem cells).
  • Currently available treatments for brain-related cancers have a low Blood Brain Barrier (BBB) transit rate, and thus have limited efficacy. There are also limited effective treatment options for lung cancers.
  • KOMIPHARM’S PAX-1 has a high 98% Blood Brain Barrier (BBB) transit rate and remains active in the brain for 72 hours to eliminate cancer stem cells. PAX-1 has also been shown to be effective in treating lung cancer, by targeting and eliminating metastatic lung cancer stem cells.

Current Status of the 14 Metastatic cancers clinical trials

  • As of August 2019, the FDA are reviewing the clinical basket trial application on 14 metastatic cancers in which 240 participants will be divided into 5 cohorts to test KOMIPHARM’S PAX-1.
  • The 14 types of metastatic cancers being researched are: non-small cell lung carcinoma, lymph non-small cell lung carcinoma, metastatic breast cancer, metastatic soft-tissue cancer, metastatic osteosarcoma, metastatic gastric cancer, metastatic renal cancer, metastatic ovarian cancer, metastatic bladder cancer, metastatic cervical cancer, metastatic endometrial cancer, metastatic head and neck cancer, metastatic prostate cancer and malignant melanoma.
  • The clinical trial is expected to commence in the second half of 2019 (prospective), where nanotechnological methods will be used to verify the extent of cancer stem cell eradication by the new drug. We are expecting highly successful results for this study, consistent with successful results of previous clinical trials.
2Phase II Clinical Trial on Glioblastoma Brain Cancer (GBM) (PJ Code: PAX-1-002)

RATIONALE

  • The World Health Organization (WHO) classifies GBM cancer as a Grade 4 malignant cancer, which is the fastest growing and most dangerous category.
  • GBM is a cancer that occurs in the brain and cancer cells are attached to neurons. As neurons cannot be directly operated on, cancer cells remain there even after surgery and treatment.
  • Mammals have a Blood Brain Barrier (BBB) which limits the absorption of many drugs entering the brain. Temozolomide (TMZ), which is the current standard treatment used in GBM only has a 20-30% BBB transition rate, limiting its efficacy.
  • KOMIPHARM’S PAX-1 has a 98% BBB transition rate due to its special Arsenic based molecular structure (MDS Pharma USA study).
  • PAX-1 has demonstrated excellent selective cancer cell eliminating capabilities in the interim results, and can greatly improve outcomes in GBM patients unresponsive to TMZ
  • PAX-1’s efficacy will be tested against 10 most prevalent GBM cell line types. The results are measured using nanotechnological methods, and PAX-1’s killing effects have been observed in all runs so far. 4 of the tests done have shown especially promising results with a high cancer cell sensitivity to PAX-1
  • Therefore, there is a high likelihood of PAX-1 becoming the standard treatment for glioblastoma brain cancer (GBM) in the future

About the Clinical Trial on GBM cancer

  • The GBM clinical trial is conducted in collaboration between the Prince of Wales Private Hospital (Sydney, Australia) and Scientia Clinical Research · The study is being led by world-renowned neurosurgeons Dr. Charlie Teo and Dr. Michael Sughrue, working together with 3 other acclaimed specialists from Scientia Clinical Research
  • The sample size is projected to be 80 patients aged 18-70, both male and female. 40 patients are newly diagnosed with GBM, and the other 40 are those who have relapsed or recurrent GBM cancer following surgery. The clinical trial is projected to submit an Orphan Drug Designation (ODD) application with the FDA during the study, and the sample size may increase with the FDA’s marketing authorisation
  • The prognosis is a high probability of cure, so the results of this study are highly anticipated in the medical community
  • GBM cancer affects 19,000 people a year in the USA alone, but it is still considered a relatively uncommon disease. PAX-1 is eligible to receive government incentives as an Orphan drug for treatment of this debilitating disease
  • KOMIPHARM has completed construction of its GMP accredited manufacturing facility and equipment
  • Therefore, following commercial manufacturing approval, KOMIPHARM expects a smooth transition to recruitment, supply and sales to countries around the world